Pharmaco-invasive strategy including Metalyse® delivers comparable clinical outcomes to primary PCI for STEMI patients

New data presented at the American College of Cardiology 62nd Annual Scientific Sessions and Expo demonstrate that patients with ST elevation acute myocardial infarction (STEMI), who cannot undergo primary percutaneous intervention (PCI) in a catheterization lab within 60 minutes of first medical contact, have similar clinical outcomes from early fibrinolysis with Metalyse® (tenecteplase, TNK-tPA) followed by timely angiography (pharmaco-invasive strategy), compared to primary PCI.1

“A significant number of patients who suffer from an acute heart attack don’t reach a cath lab within the recommended timeframe” said STREAM Principal Investigator Professor F. Van de Werf, University Hospital Gasthuisberg, Leuven, Belgium. “Prehospital fibrinolysis with timely coronary angiography, although associated with a small risk of intracranial bleeding, resulted in effective reperfusion in early presenting STEMI patients who cannot undergo primary PCI within one hour of first medical contact.”

The STREAM (STrategic Reperfusion Early After Myocardial Infarction) study is the first randomized, prospective exploratory study of a pharmaco-invasive strategy for patients with STEMI. The study evaluated the outcome of patients randomized to fibrinolysis with Metalyse®, within 3 hours of symptom onset and followed by timely angiography within 6 to 24 hours, versus primary PCI performed according to local standards.1

The primary composite endpoint of death, cardiogenic shock, congestive heart failure and reinfarction within 30 days was observed in 12.4% of patients who received Metalyse® within the pharmaco-invasive strategy including angiography within 6-24 hours, compared to 14.3% of patients who received early primary PCI (relative risk 0.86 (0.68-1.09)).1

The study results revealed no significant treatment interactions. Cardiogenic shock (4.4% vs 5.9% p=0.13) and congestive heart failure (6.1% vs 7.6% p=0.18) occurred less frequently in the pharmaco-invasive patients. For the other single clinical endpoints, namely all cause mortality (4.6 % vs 4.4% p=0.88) and reinfarction (2.5% vs 2.2% p=0.74), the rates for pharmaco-invasive arm and primary PCI respectively, were similar.2

The stroke rates (all types) were modest but strokes were significantly more frequent in the pharmaco-invasive arm (1.6% vs 0.5% p=0.03). There was no significant difference in the number of non-intracranial bleedings (6.5% in pharmaco-invasive arm vs 4.8% in PPCI, p=0.11).2

“The results from STREAM confirm that patients who receive fibrinolytic treatment, followed by angiography within 24 hours, have a similar 30 day outcome to those receiving early primary PCI” said Co-principal Investigator of STREAM, Professor A. Gershlick, University of Leicester. “These results provide a potential therapeutic option for emergency physicians and cardiologists in those patients who cannot receive primary PCI within the guideline mandated times. Despite continued global efforts to decrease time from first medical contact to primary PCI, time delays may still be present in geographically challenging areas and the pharmaco-invasive strategy should be considered in such scenarios.”

Providing early PCI can be a major operational challenge.2 Globally, PCI is not always easily or equally attainable for STEMI patients3 and a significant proportion of patients worldwide do not achieve guideline-mandated times for primary PCI.4,5

“The results of STREAM are particularly significant for patients in countries where there is a shortage of PCI facilities, as well as in areas where factors such as heavy traffic can impact the prospect of patients successfully receiving early primary PCI.” explained Dr. P. Goldstein, Emergency Physician, Lille, France. “This is an important study in the field of acute cardiac care and has confirmed that prehospital initial fibrinolysis can play a significant role in broadening the therapeutic time window for angiography to up to 24 hours in patients who cannot reach a cath lab within 60 minutes.”

About STREAM1

STREAM (STrategic Reperfusion Early After Myocardial Infarction) is an open-label, prospective, randomized, parallel, comparative, international, multicenter exploratory trial to evaluate the outcome of prehospital patients presenting with a large ST-elevation myocardial infarction within 3 hours of symptom onset. Almost 2000 patients were randomized to fibrinolysis with Metalyse® combined with enoxaparin, clopidogrel, and aspirin, and followed by timely cardiac catheterization within 6 to 24 hours, or rescue coronary intervention if reperfusion fails within 90 minutes of fibrinolysis, versus PCI performed according to local standards. Composite efficacy primary end point at 30 days included death, shock, heart failure, and reinfarction. Safety end points include ischemic stroke, intracranial hemorrhage, and major nonintracranial bleeding. Follow-up is extended to 1 year and includes all-cause mortality. STREAM excluded STEMI patients able to undergo primary PCI within 60 minutes of first medical contact.

About Metalyse®

Metalyse® (tenecteplase, TNK-tPA) is a fibrin clot dissolving drug indicated for the thrombolytic treatment of acute myocardial infarction (AMI). The efficacy of Metalyse® for the treatment of AMI has been demonstrated in approximately 20,000 patients treated with tenecteplase in monitored clinical studies (e.g. global ASSENT clinical trial programme). The European Union granted authorisation via centralised procedure for Boehringer Ingelheim’s Metalyse® on February 23, 2001. Boehringer Ingelheim is the Marketing Authorisation holder in all countries except USA, Canada and Japan. Metalyse®/TNKase® is currently authorised in 89 countries and is marketed in 86 of these.

About STEMI6

Most cases of acute myocardial infarction are caused by disruption of an atherosclerotic plaque followed by coronary thrombosis. In ST-elevation myocardial infarction (STEMI), the thrombus occludes a major epicardial coronary artery. Such an occlusion is an emergency situation, and flow to the occluded vessel should be restored as soon as possible. Various strategies for reperfusion are available, namely mechanical reperfusion by primary percutaneous coronary intervention (primary PCI) or pharmacological reperfusion by fibrinolytic therapy.

References

1. Abstract no. 302-7. Van de Werf F, Gershlick A, Goldstein P, et al. The STREAM trial. Abstract presented at American College of Cardiology 62nd Annual Scientific Sessions and Expo. 2013.
2. Armstrong PW, Gershlick AH, Goldstein P et al. Fibrinolysis or Primary PCI in ST-Elevation Myocardial Infarction. NEJM.org 2013; DOI: 10.1056/NEJMoa1301092
3. Armstrong, PW et al. The Strategic Reperfusion Early After Myocardial Infarction (STREAM) study. Amer Heart J, 2010;160(1): 30-5
4. The American Heart Association. STEMI Systems of Care. Available at: http://www.heart.org/HEARTORG/HealthcareResearch/MissionLifelineHomePage/LearnAboutMissionLifeline/STEMI-Systems-of-Care_UCM_439065_SubHomePage.jsp [Last accessed March 2013]
5. Laut KG, Pedersen AB, Lash TL, Kristensen SD. Barriers to Implementation of Primary Percutaneous Coronary Intervention in Europe. European Cardiology, 2011;7(2):108–12
6. Huber, K, Halvorsen, S. The role of fibrinolysis in the era of primary percutaneous coronary intervention. Thromb Haemost 2011; 105: 390–395